Abstract
Background:
Sickle cell disease (SCD) is a condition characterized by a prothrombotic state attributed to the simultaneous activation of hemostasis and innate immunity, referred to as thromboinflammation. Previous studies have demonstrated that the podoplanin (PDPN)/C-type lectin-like receptor-2 (CLEC-2) pathway is an emerging and important element of the pathogenesis of conditions in which inflammation and thrombosis coexist, but no data is available regarding its role in SCD.
Objectives:
To explore the PDPN/CLEC-2 pathway in SCD and correlate it with parameters of disease severity.
Methods:
Fifty SCD patients (35 with SS genotype; 15 with SC genotype) and 25 healthy individuals were recruited. PDPN and CLEC-2 were assessed for both soluble and surface expression on cells and cell aggregates, along with other classical parameters of hemostasis and platelet activation. An in vitro study was performed to analyze the effect of anti-PDPN antibody on the formation of monocyte-platelet aggregates.
Results:
Circulating levels and expression of PDPN and CLEC-2 were higher in patients with SCD, particularly in those with genotype SS. The number of CD41+CLEC+ monocytes correlated with hemoglobin, D-dimer, von Willebrand factor, and PDPN+ monocytes. In vitro, PDPN blockade reduced both monocyte-platelet aggregate formation and platelet activation. Finally, patients with a history of vaso-occlusive crises presented a trend toward increased PDPN expression in monocytes (P = .06).
Conclusion:
Our findings suggest that the PDPN/CLEC-2 pathway may play an important role in the pathogenesis of thromboinflammation in SCD, especially in patients with the SS genotype.